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Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate immune cells such as NK cells can also eliminate oncogenically transformed cells and regulate cells of the immune system. Considering NK cells as a live drug, numerous methods for the isolation and activation of NK cells have been shown to be clinically and therapeutically relevant. In such processes, various cytokines and antibodies present a source of stimulation of NK cells and enhance the efficacy of such treatments. The ex vivo expansion and activation of NK cells, along with genetic modification with CAR, enhance their antitumor activity. Recent preclinical studies have shown an antitumor effect through extracellular vesicles (EVs) derived from NK cells. Work with autologous NK cells has provided insights for clinical applications. In this review, we outline the recent advances of NK-cell-based immunotherapies, summarizing CAR-NK cells, BiKEs, and TriKEs as treatment options against cancer. This review also discusses the challenges of NK cell immunotherapy.

Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval. However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy. Additionally, we describe recent developments of novel targets for adoptive immunotherapy. Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling. We aim to shed light on the new targets focusing on acute myeloid leukemia (AML).